This application aims to investigate the phenomenon and underlying neural mechanisms of behavioral and biochemical lateralization in rats using a model of stroke. Findings obtained during the present grant period will be extended to include new techniques and indepth investigation of these phenomena. The role of specific neurotransmitter pathways in the production and maintenance of lateralized hyperactivity will be evaluated using intracortical injections of various neurotoxins. The consequences and mechanisms involved in the poststroke depletion of catecholamines will be investigated by establishing a time course of changes in the turnover of norepinephrine (NE) and dopamine (DA) in the cortex and brainstem. In addition we will determine, using knife cuts with different spatial orientations, whether transcortical pathways, cortical-subcortical or interhemispheric pathways are the essential anatomical elements disrupted by focal suction lesions which lead to lateralized hyperactivity and depletions of catecholamines. The behavior of spontaneous hyperactivity will be investigated in detail by using computer analyzed photocell chambers. In these chambers, components of activity such as exploration, habituation, rest time, circling, stereotypy, velocity and location will be related to lesion location, time since injury and degree of neurotransmitter depletion. Finally, the developmental aspect of these lateralized phenomena will be investigated by determining the age at which these phenomena can be produced and whether the time course of these neurochemical and behavioral changes are a function of the age when the lesion was produced. The major significance of this work is that it relates closely to ongoing clinical investigations of mood disorders in stroke patients as well as mechanisms of behavioral lateralization and, therefore, has important implications for both neurology and psychiatry.